Despite the prevalence and detrimental consequences of combined cocaine-heroin ("speedball") abuse, relatively little is known about the pharmacological mechanisms underlying this form of polydrug addiction Previous studies using drug discrimination techniques, a proposed model of the subjective effects of drugs, have shown that selective f opioid agonists (e g , fentanyl) can enhance the interoceptive effects of cocaine when administered in combination, yet do not consistently mimic the effects of cocaine when administered alone The present study examined the effects of heroin and its active metabolites 6-monoacetylmorphine (6-MAM) and morphine in squirrel monkeys trained to discriminate intramuscular injections of cocaine from saline Under test conditions, cocaine engendered dose-related increases in drug-lever responding, reaching nearly 100% accompanied by little change or an increase in the rate of responding Doses of heroin, 6-MAM and morphine also eng endered d ose-related increases in drug-lever responding, reaching a maximum of r 80% in most subjects and accompanied by pronounced decreases in response rate Pretreatment with the opioid antagonist naltrexone surmountably antagonized the cocaine-like effects of heroin, morphine and 6-MAM, resulting in dose-dependent shifts to the right in the opioid dose-response functions The results show that heroin, 6-MAM and morphine partially mimic the interoceptive effects of cocaine, but only at doses that suppress the rate of responding The partial cocaine-like effects of heroin, 6-MAM and morphine may be mediated via f opioid mechanisms as suggested by surmountable antagonism by naltrexone Collectively, these results suggest that at relatively high doses, cocaine and heroin share subjective effects that may, in turn, contribute to the abuse of speedball combinations in people PUBLICATIONS Rowlett, J K and Spealman, R D Opioid enhancement of the discriminative stimulus effects of cocaine Evidence for involvement of f and k opioid receptors Psychopharmacology 140 217-224, 1998